In the United States, the finish line for the pandemic as we’ve been experiencing it for the past year-plus is very much in sight — so much so that the US Centers for Disease Control and Prevention essentially said so on Thursday: Fully vaccinated people no longer need to wear masks indoors or out, or socially distance, except in a rare circumstances.
A vaccine is born
Reprinted for educational purposes and social benefit, not for profit.
Truth be told, all of the coronavirus vaccines got their start a long time before January 2020: The so-called platforms — the underlying technology — all existed before the pandemic, and all but one — the mRNA platform — had already been used commercially in the past. All of the vaccine makers had the same goal: create the best delivery system in order to trigger the strongest immune response. It’s that immune response that prepares our body so it can defend itself when it encounters the real virus later on.
That might mean using the whole virus itself, or a weakened version of it. It may mean using just a piece of the virus, or only the blueprint of a viral portion, to teach the body to recognize something foreign, and then attack it.
If you have heard anything about the Covid-19 vaccines, you have probably heard the term spike protein. Think of them as the little nubs that protrude from the surface of the coronavirus and give it its crown-like appearance. Crown — or corona, in Latin — is where this virus gets its name. The spike protein is what the virus uses to latch onto and break into our cells, which it then hijacks to replicate itself.
Viral vector vaccines such as Johnson & Johnson (Janssen), AstraZeneca/Oxford, and Russia’s Sputnik V use another virus — in this case, a common cold virus — to deliver instructions to make the spike protein, which our cells then display on their surface, triggering an immune response.
Protein subunit vaccines — such as Novavax and Sanofi — use genetically engineered insect viruses to infect moths, whose cells then produce the pieces of coronavirus spike protein. These are harvested and made into a vaccine, which is then injected into people.
The oldest vaccine technology — using the whole, killed virus to trigger an immune response — is the approach used by China’s Sinovac.
The newest type of vaccine technology is the mRNA vaccine. This method uses mRNA — messenger RNA — to give our cells the instructions to make a piece of the spike protein. Our cells then make that protein over and over again, which then stimulates our immune system to react. It’s the technology used by BioNTech, which teamed up with pharmaceutical giant Pfizer, as well as Moderna, which worked with scientists at the NIH.
The story behind mRNA technology
Many people describe mRNA technology as new, but that is not entirely true. While no mRNA medicine or therapeutic had ever been authorized by the FDA, the science behind the mRNA vaccines is based on concepts developed more than 20 years ago by Dr. Drew Weissman and Katalin Karikó, both at the University of Pennsylvania at the time. During those 20 years, mRNA vaccines have been studied and tested for conditions such as the flu, Zika and rabies, to name a few.
“DNA is the genetic code. It contains everything that makes our body and makes our body work. What RNA does, RNA makes a copy of genes — genes usually encode a protein — so the RNA makes a copy of one protein from the DNA and carries it out to a machine in the cell that makes proteins off of that RNA copy,” Weissman explained to me back in December. “We’re using the body as our protein production factory.”
Weissman said that even two decades ago, they were thinking of using mRNA technology for vaccines, as well as for therapeutic proteins, for gene editing and other applications.
Among the early adapters to study and use mRNA technology is the husband and wife team Dr. Uğur Şahin and Dr. Özlem Türeci. The couple, when they first met, bonded over science — so much so, they headed straight back to the lab after their wedding.
“We have worked hands-on and seen patients and treated patients, and at the same time we were scientists. And what we were basically daily experiencing, as cancer doctors, was that there’s not much we can offer our patients in terms of approved standards of care,” Şahin said on my podcast back in March.
“Yet in the world of science, we experienced that there were so many technologies and knowledge which would provide the opportunity to better treat patients. And this gap and the interest in translating science into survival was what we shared and why at some point we decided to do this journey together,” he said.
The pair founded BioNTech in 2008, which at the time was focused mainly on using new technologies for cancer therapies.
But then in 2020, clouds began gathering on the horizon. Even as early as January, Şahin thought the situation might develop into a pandemic, and he felt he and his wife had the tools to help. In March, BioNTech quickly teamed up with Pfizer, a company they had already been working with on other projects.
The other team working on an mRNA vaccine, Moderna, was an upstart company that had never brought an FDA-approved product to market. The company, whose name is a portmanteau of “Modified” and “RNA,” worked in partnership with the NIH’s Dr. Barney Graham and Kizzmekia Corbett, an immunologist.
Asked during an online interview Wednesday if he felt the pressure, Graham said the Vaccine Research Center, of which he is deputy director, had been under pressure before — for example, during the Ebola and Zika crises. “In this case, we started this project before it was a pandemic. So at the beginning, for us, it was a demonstration project to prove how fast we could go if the need arose. … It didn’t turn into a lot of pressure until the middle of March, when it was declared a pandemic and when we started having a lot more cases around the globe,” he said.
Hitting the jackpot
As the months of 2020 ticked by, the scientists worked almost nonstop to perfect, then test their products. And then the results started coming in. They were almost too good to be true: Early study results showed the Pfizer/BioNTech vaccine was 95% effective, and the Moderna vaccine was 94.1% effective, at preventing symptomatic Covid-19. These preliminary numbers held up as more study results came in.
At the start of the summer, the FDA had said it would require any coronavirus vaccine to be at least 50% effective to win approval (keep in mind that the flu vaccine is between 40% and 60% in years with a good match between circulating virus and the vaccine). Dr. Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases, who was then on the White House Coronavirus Task Force, said he would settle for a vaccine that was 70%-75% effective.
But the mRNA vaccines results blew all that away.
Just last week, a close friend and board member at the CDC told me, “The creators of the mRNA vaccines will likely be nominated for the Nobel prize.”
After a rapid race to the end, it was the two mRNA vaccines that crossed the finish line first and second in the United States, winning FDA emergency use authorization a week apart, in mid-December. It was just 11 months after the genetic sequence had first been shared with the world.
To reach herd immunity globally, though, all of the vaccines that make it across the finish line have a very important role to play. There will be billions of people immunized around the world, and there is a possibility that boosters will be necessary in the future as well.
The thing about races is that they force the impossible: They make us better, safer and, yes, faster than we have ever been before. And this race for a vaccine, under the brutal pressure of a pandemic, may have forever accelerated the pace of medical innovation by showing us exactly how creative, nimble and determined humankind can be.